Sinefungin VA and dehydrosinefungin V, new antitrypanosomal antibiotics produced by Streptomyces sp. K05-0178

Abstract

Two new nucleotide antibiotics, named sinefungin VA and dehydrosinefungin V, were separated by cation exchange column chromatography and purified by HPLC from the culture broth of Streptomyces sp. K05-0178, together with the known antibiotics, sinefungin, dehydrosinefungin and KSA-9342. The structures of the two novel sinefungin analogs were elucidated by spectroscopic studies, including various NMR and advanced peptide chemical methods. Sinefungin VA consists of adenosine and ornithylvalylalanine, whereas dehydrosinefungin V consists of 4′,5′-dehydroadenosine and ornithylvaline. Sinefungin VA showed potent antitrypanosomal activity with an IC50 value of 0.0026 g ml 1 in vitro without cytotoxicity against MRC-5 cells. Dehydrosinefungin V showed moderate antitrypanosomal activity (IC50=0.15 μg ml-1). © 2010 Japan Antibiotics Research Association. All rights reserved.